Transdermal drug delivery systems generally rely on passive diffusion to administer the drug while active transdermal drug delivery systems rely on an external energy source (e.g., electricity) to deliver the drug. Passive transdermal drug delivery systems are more common. Passive transdermal systems have a drug reservoir containing a high concentration of drug adapted to contact the skin where the drug diffuses through the skin and into the body tissues or bloodstream of a patient. The transdermal drug flux is dependent upon the condition of the skin, the size and physical/chemical properties of the drug molecule, and the concentration gradient across the skin. Because of the low skin permeability to many drugs, transdermal delivery has had limited applications. This low permeability is attributed primarily to the stratum corneum, the outermost skin layer which consists of flat, dead cells filled with keratin fibers (keratinocytes) surrounded by lipid bilayers. The highly-ordered structure of the lipid bilayers confers a relatively impermeable character to the stratum corneum.
One method of increasing the passive transdermal diffusional drug flux involves mechanically penetrating or disrupting the outermost skin layers thereby creating pathways into the skin in order to enhance the amount of agent being transdermally delivered. Early vaccination devices known as scarifiers generally had a plurality of tines or needles which are applied to the skin to and scratch or make small cuts in the area of application. The vaccine was applied either topically on the skin, as disclosed in Rabenau, U.S. Pat. No. 5,487,726 or as a wetted liquid applied to the scarifier tines as disclosed in Galy, U.S. Pat. No. 4,453,926, Chacornac, U.S. Pat. No. 4,109,655, and Kravitz, U.S. Pat. No. 3,136,314 or as a dry coating on and between the scarifier tines as disclosed in Kravitz U.S. Pat. No. 3,351,059. Scarifiers have been suggested for intradermal vaccine delivery in part because only very small amounts of the vaccine need to be delivered into the skin to be effective in immunizing the patient. Further, the amount of vaccine delivered is not particularly critical since an excess amount achieves satisfactory immunization as well as a minimum amount. However a serious disadvantage in using a scarifier to deliver a drug is the difficulty in determining the transdermal drug flux and the resulting dosage delivered. Also due to the elastic, deforming and resilient nature of skin to deflect and resist puncturing, very tiny (e.g., having lengths less than about 0.5 mm) skin piercing elements often do not uniformly penetrate the skin and/or are wiped free of a coating, particularly a liquid coating, of an agent upon skin penetration. Additionally, due to the self healing process of the skin, the punctures or slits made in the skin tend to close up after removal of the piercing elements from the stratum corneum. Thus, the elastic nature of the skin acts to remove active agent coating the tiny piercing elements upon penetration. Furthermore the tiny slits formed by the piercing elements heal quickly after removal of the device, thus, limiting the passage of agent through the passageways created by the piercing elements and in turn limiting the transdermal flux of such devices.
Other devices which use tiny skin piercing elements to enhance transdermal drug delivery are disclosed in European Patent EP 0407063A1, Godshall, et al. U.S. Pat. No. 5,879,326; Ganderton, et al. U.S. Pat. No. 3,814,097; Gross, et al. U.S. Pat. No. 5,279,544; Lee, et al. U.S. Pat. No. 5,250,023; Gerstel, et al. U.S. Pat. No. 3,964,482; Kravitz, et al. U.S. Pat. No. Reissue 25,637 and PCT Publication Nos. WO 96/37155, WO 96/37256, WO 96/17648, WO 97/03718, WO 98/11937, WO 98/00193, WO 97/48440, WO 97/48441, WO 97/48442, WO 98/00193, WO 99/64580, WO 98/28037, WO 98/29298, and WO 98/29365; all incorporated by reference in their entirety. These devices use piercing elements of various shapes and sizes to pierce the outermost layer (i.e., the stratum corneum) of the skin. The piercing elements disclosed in these references generally extend perpendicularly from a thin, flat member, such as a pad or sheet. The piercing elements in some of these devices are extremely small, some having dimensions (i.e., a microprojection length and width) of only about 25-400 μm and a mircorprojection thickness of only about 5-50 μm. These tiny piercing/cutting elements make correspondingly small microslits/microcuts in the stratum corneum for enhanced transdermal agent delivery therethrough.
More recently, Cormier et al., in U.S. patent application Ser. No. 10/045,842 filed Oct. 26, 2001 disclose a device for transdermally delivering a potent drug. The device has a plurality of skin piercing microprojections which have a dry coating of the drug. Cormier et al. disclose microfluidic coating techniques such as ink jet printing to selectively coat the drug only on the skin piercing microprojections rather than on other portions/surfaces of the device which do not penetrate into the skin. In spite of these disclosures, Cormier et al. do not address the difficulties in aiming the microfluidic spray or deposit only onto the portions of the device which pierce the skin. Thus, there is a need for a precisely controlled coating method which can reproducibly, and at high volumes, coat only the skin-piercing portions of such devices.